Standardization of an antiviral pipeline for human norovirus in human intestinal enteroids demonstrates nitazoxanide has no to weak antiviral activity

• Published in: Antimicrobial agents and chemotherapy Vol. 67; no. 10; p. e0063623
• Main Authors: Lewis, Miranda A, Cortés-Penfield, Nicolás W, Ettayebi, Khalil, Patil, Ketki, Kaur, Gurpreet, Neill, Frederick H, Atmar, Robert L, Ramani, Sasirekha, Estes, Mary K
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 18-10-2023
• Subjects: Antiviral Agents; Antiviral Agents - pharmacology; Antiviral Agents - therapeutic use; Caliciviridae Infections - drug therapy; Gastroenteritis - drug therapy; Humans; Norovirus; Reference Standards; Virus Replication; genotypes; nitazoxanide; antivirals; intestinal organoids; human norovirus; enteroids
• ISSN: 0066-4804; 1098-6596
• DOI: 10.1128/aac.00636-23

Human noroviruses (HuNoVs) are the leading cause of acute gastroenteritis. In immunocompetent hosts, symptoms usually resolve within 3 days; however, in immunocompromised persons, HuNoV infection can become persistent, debilitating, and sometimes life-threatening. There are no licensed therapeutics for HuNoV due to a near half-century delay in its cultivation. Treatment for chronic HuNoV infection in immunosuppressed patients anecdotally includes nitazoxanide, a broad-spectrum antimicrobial licensed for treatment of parasite-induced gastroenteritis. Despite its off-label use for chronic HuNoV infection, nitazoxanide has not been clearly demonstrated to be an effective treatment. In this study, we standardized a pipeline for antiviral testing using multiple human small intestinal enteroid lines representing different intestinal segments and evaluated whether nitazoxanide inhibits replication of five HuNoV strains
. Nitazoxanide did not exhibit high selective antiviral activity against any HuNoV strain tested, indicating it is not an effective antiviral for HuNoV infection. Human intestinal enteroids are further demonstrated as a model to serve as a preclinical platform to test antivirals against HuNoVs to treat gastrointestinal disease. Abstr.